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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02729051




Registration number
NCT02729051
Ethics application status
Date submitted
31/03/2016
Date registered
6/04/2016
Date last updated
15/07/2019

Titles & IDs
Public title
Comparative Study of Fluticasone Furoate(FF)/Umeclidinium Bromide (UMEC)/ Vilanterol (VI) Closed Therapy Versus FF/VI Plus UMEC Open Therapy in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Scientific title
A Phase IIIB, 24-week Randomised, Double-blind Study to Compare 'Closed' Triple Therapy (FF/UMEC/VI) With 'Open' Triple Therapy (FF/VI + UMEC), in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Secondary ID [1] 0 0
2015-005212-14
Secondary ID [2] 0 0
200812
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FF/UMEC/VI
Treatment: Drugs - FF/VI
Treatment: Drugs - UMEC
Treatment: Drugs - Placebo
Treatment: Drugs - Albuterol/salbutamol

Experimental: FF/UMEC/VI closed triple therapy plus Placebo - Subjects will receive FF/UMEC/VI, 100 mcg/62.5 mcg/25 mcg and placebo inhalation powder via the dry powder inhaler (DPI), once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.

Active Comparator: FF/VI plus UMEC open triple therapy - Subjects will receive FF/VI, 100 mcg/25 mcg and UMEC, 62.5 mcg inhalation powder via the DPI, once daily in the morning. Subjects will also receive albuterol/salbutamol as a rescue medication when needed during the treatment period.


Treatment: Drugs: FF/UMEC/VI
This intervention is provided in two strips. First strip contains FF blended with lactose. It is available as dry white powder, 100 mcg per blister. Second strip contains UMEC and VI blended with lactose and magnesium stearate. It is available as dry white powder, 62.5 mcg per blister UMEC, 25 mcg per blister VI. The intervention is inhaled via the DPI, once daily in the morning. DPI contains 30 doses (2 strips with 30 blisters per strip).

Treatment: Drugs: FF/VI
This intervention is provided in two strips. First strip contains FF blended with lactose. It is available as dry white powder, 100 mcg per blister. Second strip contains VI blended with lactose and magnesium stearate. It is available as dry white powder, 25 mcg per blister. The intervention is inhaled via the DPI, once daily in the morning. DPI contains 30 doses (2 strips with 30 blisters per strip).

Treatment: Drugs: UMEC
This intervention is available in one strip. The strip contains UMEC blended with lactose and magnesium stearate. The formulation is available as dry white powder, 62.5 mcg per blister. The intervention is inhaled via the DPI, once daily in the morning. DPI contains 30 doses (1 strip with 30 blisters).

Treatment: Drugs: Placebo
This intervention is available in one strip. The strip contains lactose. The formulation is available as dry white powder. The intervention is inhaled via the DPI, once daily in the morning. DPI contains 30 doses (1 strip with 30 blisters).

Treatment: Drugs: Albuterol/salbutamol
This is a rescue medication administered via metered-dose inhaler (MDI) with a spacer which will be used when needed during the study.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24 - FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. It was measured using centralized spirometry. FEV1 values at Week 0, pre-dose were considered as Baseline values. Change from Baseline was calculated by subtracting Baseline value from the value at indicated time point. Modified Per Protocol (mPP) Population was used which comprised of all participants in the Intent-to-Treat (ITT) Population, who do not have a full protocol deviation considered to impact efficacy. Data following a moderate/severe COPD exacerbation or pneumonia was excluded from analysis due to the potential impact of the exacerbation or the medications used to treat it. Participants with partial protocol deviations considered to impact efficacy were included in the mPP Population but had their data excluded from analysis from the time of deviation onwards. Analysis was performed using a mixed model repeated measures (MMRM) method.
Timepoint [1] 0 0
Baseline and Week 24
Secondary outcome [1] 0 0
Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire (SGRQ) Total Score at Week 24 - SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on health related quality of life (HRQoL) of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Response was defined as an SGRQ total score of >=4 units below Baseline. Non response was defined as a SGRQ total score <4 units below Baseline or a missing SGRQ total score with no subsequent on treatment scores. ITT Population comprised of randomized participants, excluding those who were randomized in error. A participant screened or run-in failure and also randomized was considered to be randomized in error. Analysis was performed using a generalized linear mixed model with a logit link function.
Timepoint [1] 0 0
Week 24
Secondary outcome [2] 0 0
Change From Baseline in SGRQ Total Score at Week 24 - SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Values at Week 0, pre-dose were considered as Baseline values. Change from Baseline was calculated by subtracting Baseline value from the value at indicated time point. Analysis was performed using a MMRM method including covariates of Baseline SGRQ Total score, stratum (number of long-acting bronchodilators per day during the run-in: 0/1 or 2), visit, geographical region, treatment, visit by treatment and visit by Baseline interaction.
Timepoint [2] 0 0
Baseline and Week 24
Secondary outcome [3] 0 0
Percentage of Responders Based on Transitional Dyspnea Index (TDI) Focal Score at Week 24 - The TDI measures changes in the participant's dyspnea. TDI focal score was calculated as the sum of the ratings recorded for each of the 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6. lower scores indicating more impairment. TDI focal score was calculated as the sum of the 3 individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). The lower the score, the more deterioration in severity of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. A participant was considered as a responder if the on-treatment TDI focal score was at least 1 unit at that visit. Non-response was defined as a TDI focal score of less than 1 unit or a missing TDI focal score with no subsequent non-missing on-treatment scores. Analysis was performed using a generalized linear mixed model with a logit link function.
Timepoint [3] 0 0
Week 24
Secondary outcome [4] 0 0
TDI Focal Score at Week 24 - The TDI measures changes in the participant's dyspnoea. TDI focal score was calculated as the sum of the ratings recorded for each of the 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6. lower scores indicating more impairment. TDI focal score was calculated as the sum of the 3 individual scores and then divided by 2 (so the range of the TDI focal score is -9 to +9). The lower the score, the more deterioration in severity of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. Analysis was performed using a repeated measures model.
Timepoint [4] 0 0
Week 24
Secondary outcome [5] 0 0
Time to First Moderate or Severe Exacerbation - COPD exacerbations were identified based on the investigator's clinical judgment. Worsening symptoms of COPD that required treatment with oral/systemic corticosteroids and/or antibiotics were considered as moderate exacerbation. Worsening symptoms of COPD that required treatment with in-subject hospitalization was considered as severe exacerbation. Hazard ratio and 95% confidence interval (CI) is from a Cox proportional hazards model with covariates of treatment group, sex, exacerbation history (0, 1, >=2 moderate/severe exacerbations, prior year), smoking status (screening), stratum (number of long-acting bronchodilators per day during the run-in: 0/1 or 2), geographical region and percent predicted FEV1 at Baseline. Median and inter-quartile range (first and third quartile) have been presented.
Timepoint [5] 0 0
Up to 25 weeks

Eligibility
Key inclusion criteria
Informed Consent: A signed and dated written informed consent prior to study participation.

- Type of subject: Outsubject.

- Age: Subjects 40 years of age or older at Screening (Visit 1).

- Gender: Male or female subjects. A female subject is eligible to participate if she is
not pregnant (as confirmed by a negative urine human chorionic gonadotrophin (hCG)
test), not lactating, and at least one of the following conditions applies:

Non-reproductive potential defined as:

- Pre-menopausal females with one of the following: Documented tubal ligation,
Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of
bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy.

- Postmenopausal defined as 12 months of spontaneous amenorrhea. Females on hormone
replacement therapy (HRT) and whose menopausal status is in doubt will be required to
use one of the highly effective contraception methods if they wish to continue their
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of
post-menopausal status prior to study enrolment.

Reproductive potential and agrees to follow one of the options listed in the Modified List
of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential
(FRP) from 30 days prior to the first dose of study treatmentand until after the last dose
of study treatmentand completion of the follow-up visit.

- COPD Diagnosis: An established clinical history of COPD in accordance with the
definition by the American Thoracic Society/European Respiratory Society.

- Smoking History: Current or former cigarette smokers with a history of cigarette
smoking of >=10 pack-years at Screening (Visit 1) [number of pack years = (number of
cigarettes per day divided by 20) x number of years smoked (e.g., 20 cigarettes per
day for 10 years, or 10 cigarettes per day for 20 years)]. Previous smokers are
defined as those who have stopped smoking for at least 6 months prior to Screening
(Visit 1). Note: Pipe and/or cigar use cannot be used to calculate pack-year history.

- Severity of COPD symptoms: A score of >=10 on the COPD Assessment Test (CAT) at
Screening (Visit1).

- Severity of COPD Disease: A post-albuterol/salbutamol FEV1/FVC ratio of <0.70 at
Screening (Visit 1).

- Existing COPD maintenance treatment: Subject must be receiving daily maintenance
treatment for their COPD for at least 3 months prior to Screening (Visit 1). Note:
Subjects receiving only as needed COPD medications are not eligible.

- History of Exacerbations: Subjects must demonstrate: a post-bronchodilator FEV1 <50
percent predicted normal at Screening (Visit 1) and a documented history of >=1
moderate or severe COPD exacerbation in the 12 months prior to Screening or a
post-bronchodilator 50 percent =< FEV1 <80 percent predicted normal at Screening
(Visit 1) and a documented history of >=2 moderate exacerbations or a documented
history of >=1 severe COPD exacerbation (hospitalised) in the 12 months prior to
Screening (Visit 1). Notes: Percent predicted will be calculated using the European
Respiratory Society Global Lung Function Initiative reference equations; A documented
history of a COPD exacerbation (e.g., medical record verification) is a medical record
of worsening COPD symptoms that required systemic/oral corticosteroids and/or
antibiotics (for a moderate exacerbation) or hospitalisation (for a severe
exacerbation). Prior use of antibiotics alone does not qualify as an exacerbation
history unless the use was associated with treatment of worsening symptoms of COPD,
such as increased dyspnoea, sputum volume, or sputum purulence (colour). Subject
verbal reports are not acceptable.

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category.
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant
during the study.

- Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of
asthma are eligible if they have a current diagnosis of COPD, which is the primary
cause of their respiratory symptoms).

- Alpha 1-antitrypsin deficiency: Subjects with alpha1-antitrypsin deficiency as the
underlying cause of COPD.

- Other respiratory disorders: Subjects with active tuberculosis are excluded. Subjects
with other respiratory disorders (e.g. clinically significant: bronchiectasis,
sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases) are
excluded if these conditions are the primary cause of their respiratory symptoms.

- Lung resection: Subjects with lung volume reduction surgery (including procedures such
as endobronchial valves) within the 12 months prior to Screening (Visit 1).

- Risk Factors for Pneumonia: immune suppression (e.g. advanced human immune deficiency
virus (HIV) with high viral load and low cluster of differentiation 4 (CD4) count,
Lupus on immunosuppressants that would increase risk of pneumonia) or other risk
factors for pneumonia (e.g. neurological disorders affecting control of the upper
airway, such as Parkinson's Disease, Myasthenia Gravis). Notes: Subjects at a high
risk for pneumonia (e.g. very low body mass index (BMI), severely malnourished or very
low FEV1) will only be included at the discretion of the investigator.

- Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least
14 days prior to Screening (Visit 1) and at least 30 days following the last dose of
oral/systemic corticosteroids (if applicable).

- Other Respiratory tract infections that have not resolved at least 7 days prior to
Screening (Visit 1).

- Abnormal Chest x-ray: Chest x-ray reveals evidence of pneumonia or a clinically
significant abnormality not believed to be due to the presence of COPD, or another
condition that would hinder the ability to detect an infiltrate on chest x-ray (e.g.
significant cardiomegaly, pleural effusion or scarring). All subjects will have a
chest x-ray at Screening (Visit 1) [or historical radiograph or computerised
tomography (CT) scan obtained within 3 months prior to Screening (Visit 1). Notes:
Subjects who have experienced pneumonia and/or moderate or severe COPD exacerbation
within 3 months of Screening (Visit 1) must provide a post pneumonia/exacerbation
chest x-ray or have a chest x-ray conducted at Screening (Visit 1); For sites in
Germany: If a chest x-ray (or CT scan) within 3 months prior to Screening (Visit 1) is
not available, approval to conduct a diagnostic chest x-ray will need to be obtained
from the Federal Office for Radiation Protection (BFS).

- Other diseases/abnormalities: Subjects with historical or current evidence of
clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,
immunological, gastrointestinal, urogenital, nervous system, musculoskeletal, skin,
sensory, endocrine (including uncontrolled diabetes or thyroid disease) or
hematological abnormalities that are uncontrolled. Significant is defined as any
disease that, in the opinion of the investigator, would put the safety of the subject
at risk through participation, or which would affect the efficacy or safety analysis
if the disease/condition exacerbated during the study.

- Unstable liver disease: ALT >2 times upper limit of normal (ULN); and bilirubin >1.5
times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is
fractionated and direct bilirubin <35 percent). Current active liver or biliary
disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or
otherwise stable chronic liver disease per investigator assessment). Notes: Stable
chronic liver disease should generally be defined by the absence of ascites,
encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or
persistent jaundice, or cirrhosis; Chronic stable hepatitis B and C (e.g., presence of
hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at
screening or within 3 months prior to first dose of study treatment) are acceptable if
subject otherwise meets entry criteria.

- Unstable or life threatening cardiac disease: subjects with any of the following at
Screening (Visit 1) would be excluded: Myocardial infarction or unstable angina in the
last 6 months; Unstable or life threatening cardiac arrhythmia requiring intervention
in the last 3 months; New York Heart Association (NYHA) Class 4 Heart failure.

- Abnormal and clinically significant 12-Lead ECG finding: Investigators will be
provided with ECG reviews conducted by a centralized independent cardiologist to
assist in evaluation of subject eligibility. The investigator will determine the
clinical significance of each abnormal ECG finding in relation to the subject's
medical history and exclude subjects who would be at undue risk by participating in
the trial. An abnormal and clinically significant finding that would preclude a
subject from entering the trial is defined as a 12-lead tracing that is interpreted
as, but not limited to, any of the following: atrial fibrillation (AF) with rapid
ventricular rate >120 beats per minute (BPM); sustained or nonsustained ventricular
tachycardia (VT); Second degree heart block Mobitz type II and third degree heart
block (unless pacemaker or defibrillator had been inserted).

- Contraindications: A history of allergy or hypersensitivity to any corticosteroid,
anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or
magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic
hypertrophy or bladder neck obstruction that, in the opinion of the investigator
contraindicates study participation.

- Cancer: Subjects with carcinoma that has not been in complete remission for at least 3
years. Subjects who have had carcinoma in situ of the cervix, squamous cell carcinoma
and basal cell carcinoma of the skin would not be excluded based on the 3 year waiting
period if the subject has been considered cured by treatment.

- Oxygen therapy: Use of long-term oxygen therapy (LTOT) described as resting oxygen
therapy >3 Liters per minute (Oxygen use <= 3 Liters/minute flow is not exclusionary.)

- Medication prior to spirometry: Subjects who are medically unable to withhold their
albuterol/salbutamol for the 4-hour period required prior to spirometry testing at
each study visit.

- Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug
abuse within the last 2 years.

- Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study
procedures. Any infirmity, disability, or geographic location that would limit
compliance for scheduled visits.

- Questionable validity of consent: Subjects with a history of psychiatric disease,
intellectual deficiency, poor motivation or other conditions that will limit the
validity of informed consent to participate in the study.

- Affiliation with investigator site: Study investigators, sub-investigators, and study
coordinators, employees of a participating investigator or study site, or immediate
family members of the aforementioned that is involved with this study.

- Inability to read: In the opinion of the investigator, any subject who is unable to
read and/or would not be able to complete study related materials.

- Medication prior to Screening: Use of the following medications within 30 days prior
to Screening (Visit 1) or requirement for their use during the study: Use of long term
continuous antibiotic therapy; systemic, oral, parenteral corticosteroids
(Intra-spinal and intra-articular injections are allowed); use of any other
investigational drug: within 30 days or 5 half lives whichever is longer.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Coffs Harbour
Recruitment hospital [2] 0 0
GSK Investigational Site - Maroubra
Recruitment hospital [3] 0 0
GSK Investigational Site - Randwick
Recruitment hospital [4] 0 0
GSK Investigational Site - Westmead
Recruitment hospital [5] 0 0
GSK Investigational Site - Woodville South
Recruitment hospital [6] 0 0
GSK Investigational Site - Footscray
Recruitment hospital [7] 0 0
GSK Investigational Site - Murdoch
Recruitment hospital [8] 0 0
GSK Investigational Site - Golden Beach
Recruitment postcode(s) [1] 0 0
2450 - Coffs Harbour
Recruitment postcode(s) [2] 0 0
2035 - Maroubra
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
5011 - Woodville South
Recruitment postcode(s) [6] 0 0
3011 - Footscray
Recruitment postcode(s) [7] 0 0
6150 - Murdoch
Recruitment postcode(s) [8] 0 0
4551 - Golden Beach
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Buenos Aires
Country [2] 0 0
Argentina
State/province [2] 0 0
Ciudad Autónoma de Buenos Aires
Country [3] 0 0
Argentina
State/province [3] 0 0
Mendoza
Country [4] 0 0
Argentina
State/province [4] 0 0
San Miguel de Tucumán
Country [5] 0 0
France
State/province [5] 0 0
Brest Cedex
Country [6] 0 0
France
State/province [6] 0 0
Marseille cedex 03
Country [7] 0 0
France
State/province [7] 0 0
Nantes cedex 2
Country [8] 0 0
France
State/province [8] 0 0
Perpignan
Country [9] 0 0
France
State/province [9] 0 0
Pringy Cedex
Country [10] 0 0
France
State/province [10] 0 0
Toulouse
Country [11] 0 0
Germany
State/province [11] 0 0
Bayern
Country [12] 0 0
Germany
State/province [12] 0 0
Brandenburg
Country [13] 0 0
Germany
State/province [13] 0 0
Hessen
Country [14] 0 0
Germany
State/province [14] 0 0
Niedersachsen
Country [15] 0 0
Germany
State/province [15] 0 0
Nordrhein-Westfalen
Country [16] 0 0
Germany
State/province [16] 0 0
Sachsen
Country [17] 0 0
Italy
State/province [17] 0 0
Campania
Country [18] 0 0
Italy
State/province [18] 0 0
Emilia-Romagna
Country [19] 0 0
Italy
State/province [19] 0 0
Sicilia
Country [20] 0 0
Italy
State/province [20] 0 0
Toscana
Country [21] 0 0
Italy
State/province [21] 0 0
Umbria
Country [22] 0 0
Japan
State/province [22] 0 0
Aichi
Country [23] 0 0
Japan
State/province [23] 0 0
Chiba
Country [24] 0 0
Japan
State/province [24] 0 0
Ehime
Country [25] 0 0
Japan
State/province [25] 0 0
Fukuoka
Country [26] 0 0
Japan
State/province [26] 0 0
Gifu
Country [27] 0 0
Japan
State/province [27] 0 0
Gunma
Country [28] 0 0
Japan
State/province [28] 0 0
Hokkaido
Country [29] 0 0
Japan
State/province [29] 0 0
Hyogo
Country [30] 0 0
Japan
State/province [30] 0 0
Ibaraki
Country [31] 0 0
Japan
State/province [31] 0 0
Ishikawa
Country [32] 0 0
Japan
State/province [32] 0 0
Kagawa
Country [33] 0 0
Japan
State/province [33] 0 0
Kanagawa
Country [34] 0 0
Japan
State/province [34] 0 0
Kyoto
Country [35] 0 0
Japan
State/province [35] 0 0
Mie
Country [36] 0 0
Japan
State/province [36] 0 0
Niigata
Country [37] 0 0
Japan
State/province [37] 0 0
Okayama
Country [38] 0 0
Japan
State/province [38] 0 0
Osaka
Country [39] 0 0
Japan
State/province [39] 0 0
Shizuoka
Country [40] 0 0
Japan
State/province [40] 0 0
Tokyo
Country [41] 0 0
Korea, Republic of
State/province [41] 0 0
Seoul
Country [42] 0 0
Korea, Republic of
State/province [42] 0 0
Suwon
Country [43] 0 0
Korea, Republic of
State/province [43] 0 0
Wonju, Gangwon-do,
Country [44] 0 0
Mexico
State/province [44] 0 0
Estado De México
Country [45] 0 0
Mexico
State/province [45] 0 0
Jalisco
Country [46] 0 0
Mexico
State/province [46] 0 0
Nuevo León
Country [47] 0 0
Mexico
State/province [47] 0 0
Aguascalientes
Country [48] 0 0
Mexico
State/province [48] 0 0
México DF
Country [49] 0 0
Poland
State/province [49] 0 0
Elblag
Country [50] 0 0
Poland
State/province [50] 0 0
Grudziadz
Country [51] 0 0
Poland
State/province [51] 0 0
Kielce
Country [52] 0 0
Poland
State/province [52] 0 0
Krakow
Country [53] 0 0
Poland
State/province [53] 0 0
Ostrow Wilekopolski
Country [54] 0 0
Poland
State/province [54] 0 0
Tarnów
Country [55] 0 0
Romania
State/province [55] 0 0
Bucharest
Country [56] 0 0
Romania
State/province [56] 0 0
Cluj Napoca
Country [57] 0 0
Romania
State/province [57] 0 0
Ramnicu Valcea
Country [58] 0 0
Romania
State/province [58] 0 0
Suceava
Country [59] 0 0
Romania
State/province [59] 0 0
Targu Mures
Country [60] 0 0
Romania
State/province [60] 0 0
Timisoara
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Arkhangelsk
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Barnaul
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Irkutsk
Country [64] 0 0
Russian Federation
State/province [64] 0 0
Izhevsk
Country [65] 0 0
Russian Federation
State/province [65] 0 0
Kazan
Country [66] 0 0
Russian Federation
State/province [66] 0 0
Moscow
Country [67] 0 0
Russian Federation
State/province [67] 0 0
Novosibirsk
Country [68] 0 0
Russian Federation
State/province [68] 0 0
Saint Petesburg
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Saint-Petersburg
Country [70] 0 0
Russian Federation
State/province [70] 0 0
Saratov
Country [71] 0 0
Russian Federation
State/province [71] 0 0
Tomsk
Country [72] 0 0
Russian Federation
State/province [72] 0 0
Ufa
Country [73] 0 0
Spain
State/province [73] 0 0
Cantabria
Country [74] 0 0
Spain
State/province [74] 0 0
Barcelona
Country [75] 0 0
Spain
State/province [75] 0 0
Mérida (Badajoz)
Country [76] 0 0
Spain
State/province [76] 0 0
Pamplona
Country [77] 0 0
Spain
State/province [77] 0 0
Pozuelo De Alarcón/Madrid
Country [78] 0 0
Spain
State/province [78] 0 0
Zaragoza

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This multicenter study will be conducted to compare the effect of FF/UMEC/VI with FF/VI plus
UMEC on lung function after 24 weeks of treatment. This is a phase IIIB, 24-week, randomized,
double-blind, parallel group multicenter study. This study will test the hypothesis that the
difference in trough forced expiratory volume in one second (FEV1) between treatment groups
is less than or equal to a pre-specified non-inferiority margin. Alternatively, this study
will also test the hypothesis that the difference between treatment groups is greater than
the margin. The triple therapy of FF/UMEC/VI in a single inhaler is being developed with the
aim of providing a new treatment option for the management of advanced Global Initiative for
Chronic Obstructive Lung Disease (GOLD) Group D COPD which will reduce the exacerbation
frequency, allow for a reduced burden of polypharmacy, convenience, and improve lung
function, health related quality of life (HRQoL) and symptom control over established
dual/monotherapies. This study has a 2 week run in period where subjects will continue to
have their existing COPD medications. At randomization, subjects will discontinue all
existing COPD medications and will be assigned to treatment of FF/UMEC/VI, 100 microgram
(mcg)/62.5 mcg/25 mcg and placebo or FF/VI, 100 mcg/25 mcg and UMEC, 62.5 mcg in a 1:1 ratio
for 24 weeks. Subjects will have clinical visits at Pre-Screening (Visit 0), Screening (Visit
1), Randomization (Week 0, Visit 2), Week 4 (Visit 3), Week 12 (Visit 4) and Week 24 (Visit
5). A follow-up visit will be conducted at 1 week after the end of treatment period or after
early withdrawal visit. Approximately, 1020 subjects will be enrolled in this study. There
will be two pharmacokinetic (PK) groups (subset A and subset B). Approximately 120 subjects
will be assigned to subset A and approximately 60 subjects will be assigned to subset B. The
total duration of subject participation will be approximately 27 weeks, consisting of a
2-week run-in period, 24-week treatment period and a 1-week follow-up period.
Trial website
https://clinicaltrials.gov/show/NCT02729051
Trial related presentations / publications
Bremner PR, Birk R, Brealey N, Ismaila AS, Zhu CQ, Lipson DA. Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study. Respir Res. 2018 Jan 25;19(1):19. doi: 10.1186/s12931-018-0724-0.
Public notes

Contacts
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GSK Clinical Trials
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GlaxoSmithKline
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Summary results
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